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    The effect of polymorphisms in the promoter region of the MMP-1 gene on the occurrence and invasiveness of hypophyseal adenoma
    (Springer Wien, 2010) Altas, Murat; Bayrak, Omer Faruk; Ayan, Erdogan; Bolukbasi, Fatihhan; Silav, Gokalp; Coskun, Kerim Kenan; Culha, Mustafa
    The matrix metalloproteinase-1 enzyme (MMP-1, also called collagenase 1) plays a key role in turnover of collagen fibers in the intercellular matrix. Insertion of a guanine residue was found within the promoter region of the MMP-1 gene. We found that MMP-1 levels increased approximately twofold over normal when this insertion was present, enabling MMP-1 to facilitate tumor invasion and metastasis. MMP-1 is also believed to play a role in tumor development. The aim of our study is to investigate the effect of polymorphisms in the promoter region of the MMP-1 gene on the development of benign and invasive hypophyseal adenomas. Thirty patients with hypophyseal adenomas diagnosed by radiological examination underwent surgical removal, and the diagnosis was confirmed using immunohistochemical staining of the pathology specimens. We found that ten of these patients had invasive adenomas confirmed by radiological examination and immunohistochemical staining. DNA isolation was performed on all specimens, and 5-cc venous blood samples were obtained from all patients as well as 30 volunteers using the Qiagen QIAquick kit. Promoter regions of MMP-1 genes from the DNA samples were amplified using polymerase chain reaction (PCR) and primers designed for the site-directed mutation method. Following PCR, a guanine residue within the promoter region of the MMP-1 gene was identified using the restriction fragment length polymorphism method and the ALU I restriction enzyme. Three genotypes were detected in a genotyping assay: 2G/2G, 1G/2G, and 1G/1G. Of the surgically treated patients, 36.6% had the 2G/2G genotype, 46.6% had the 1G/2G genotype, and 16.6% had the 1G/1G genotype. The 2G allele frequency was found to be 83.4%. In 90% of cases of invasive adenoma, a homozygous 2G/2G genotype was detected. The risk for development of hypophyseal adenoma may be greater in patients with the 2G allele. In cases of existing hypophyseal adenoma, those with the homozygous 2G allele tend to be invasive.
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    The Expression of MMP-11 In Benign Meningiomas
    (Journal Neurological Sciences, 2014) Ayan, Erdogan; Uyar, Suheyla Bozkurt; Cerci, Ajlan; Altas, Murat; Bolukbasi, Fatihhan; Elmaci, Ilhan; Sav, Aydin
    The WHO categorises tumours based on their histological properties; however, this classification falls short of understanding their biological behaviours. Recently, there has been an increase in the number of studies on extracellular matrix components with the aim of understanding the biological behaviours of tumours. MMP-11 is a metalloproteinase from the MMP family that has a different expression pattern, mechanism of action, and substrate range compared with the other members of this family. Of the 55 benign meningioma cases examined, 29 were transitional, 16 were meningothelial, and 8 were fibroblastic in nature. In the meningotheliomatous cases, the MMP-11 expression score was high (75%), whereas it was low in the fibrous cases (87.5%). The Ki-67 levels in the cases with high MMP-11 expression scores were significantly higher than those of cases with low MMP-11 expression scores. Although there was no statistically significant correlation between recurrence and the MMP-11 expression score, 5 out of 7 cases with recurrence were found to have high MMP-11 expression scores. According to our study, MMP-11 is expressed in Grade I meningiomas. The level of MMP-11 expression appears to be high in the meningotheliomatous tumours and low in the fibrous subtypes. The tumours with a high level of MMP-11 expression also demonstrated high Ki-67 values.